The decline of bone mass associated with aging is a well documented phenomena. An acceleration of this process can lead to the syndrome of osteoporosis. The primary defect could be associated with the inability of osteoblasts to cope with the need to generate calcifiable matrix. Our working hypothesis is that a defect in the conversion of stem cells into osteoblasts, leading to a net decline of bone producing cells, is the root of the problem. If this is due to a lack of osteoprogenitor cells per se, or to an interferance with the process of stem cell differentiation, may become apparent from the work proposed. We shall investigate "in vitro", and by using various animal models (old animals, hormone induced osteoporosis, irradiated animals) the factors associated with the conversion of bone marrow cells into bone producing cells. Various parameters will be investigated to establish the metabolic activity of these cells. Fibronectin is the first detectable entity that accumulates at the site of bone induction. We shall follow by studying collagen synthesis (types of collagen, appearance of crosslinking precursors and crosslinks, and post-ribosomal modifications) sulfate uptake, cell proliferation using isotope markers and light and electron microscopy. We shall identify bone specific markers such as -carboxyglutamate containing proteins (osteocalcin) and alkaline phosphatase. We expect that the experimental approach developed will provide useful information for understanding other age-related degenerative diseases of the connective tissues.